Postural tachycardia syndrome
(POTS) is characterized by exercise intolerance and sympathoactivation.
To examine whether abnormal cardiac output and central blood volume
changes occur during exercise in POTS, we studied 29 patients with POTS
(17-29years) and 12 healthy subjects (18-27 years) using impedance and
venous occlusion plethysmography to assess regional blood volumes and
flows during supine static handgrip to evoke the exercise pressor
reflex. POTS was subgrouped into normal and low flow groups based on
calf blood flow. WE examined autonomic effects with variability
techniques. During handgrip systolic BP increased from 112±4 to 139±9
mmHg in control from 119±6 to 143±9 in normal flow POTS, but only from
117±4 to 128±6 in low flow POTS. Heart rate increased from 63±6 to 82±4
bpm in control, 76±3 to 92±6 in normal flow POTS, and 88±4 to 100±6 in
low flow POTS. Heart rate variability and coherence markedly decreased
in low flow POTS indicating uncoupling of baroreflex heart rate
regulation. The increase in central blood volume with handgrip was
absent in low flow and blunted in normal flow POTS associated with
abnormal splanchnic emptying. Cardiac output increased in control, was
unchanged in low flow and was attenuated in normal flow POTS. Total
peripheral resistance was increased compared to control in all POTS. The
exercise pressor reflex is attenuated in low flow POTS. While increased
cardiac output and central blood volume characterizes controls,
increased peripheral resistance with blunted or eliminated i central
blood volume increments characterize POTS and may contribute to exercise
intolerance.

Table 2 Heart
Rate and Blood Pressure Variability

Baseline

1 min

2 min

1&2 min

Recovery

Total HRV
Power (TP, ms2/Hz)

Control

Low Flow

Normal Flow

3213±836

837±162†

1689±380

1683±714

1080±366

2273±565

2207±1156*

1004±276†

1973±463

2156±895*

980±299†

2094±275

3245±906

1682±616*†

2120±503

Low
Frequency (LF, 0.04-0.15Hz) HRV Power (ms2/Hz)

Control

Low Flow

Normal Flow

1071±310

198±44†

555±124†

562±279*

415±169*

468±107

1061±710

294±61†

573±133†

769±326

301±108†

383±65†

1197±367

593±194*†

768±193

High
Frequency (HF, 0.2-0.5 Hz) HRV Power (ms2/Hz)

Control

Low Flow

Normal Flow

1476±498

216±64†

589±204

827±417

485±197*

1567±435*†

847±389

556±181*

1205±338*

843±377

407±127*

845±207

1546±423

898±390*

1093±276*

LF/HF Ratio

Control

Low Flow

Normal Flow

0.90±.19

1.18±0.21

1.33±.18

0.80±.17

0.87±.16

0.38±.04*†

1.76±.63*

1.1±.29

0.83±.26†

1.02±.31

0.81±.11

0.62±.11

1.12±0.20

1.06±0.31

1.09±0.17

Total BPV
Power (mmHg2/Hz)

Control

Low Flow

Normal Flow

8.4±2.0

10.2±2.0

12.5±2.4

6.8±0.8*

7.1±2.0*

12.8±8

9.8±1.5*

6.9±1.3*†

13.4±4.3†

9.5±1.6

8.0±2.0

10.6±2.6

10.0±2.3

6.7±2.1†

7.5±1.8

Transfer
Coherence

Control

Low Flow

Normal Flow

0.76±0.10

0.36±.05†

0.7±.04

0.41±.06*

0.3±.07*

0.3±.06*

0.26±.05*

0.30±.07*

0.22±.06*

0.34±.05*

0.23±.06*

0.24±.04*

0.42±.06*

0.17±.04*†

0..20±.05*†

Transfer
Magnitude (gain/ms/mmHg)

Control

Low Flow

Normal Flow

18±2

8±2†

13±2

11±2*

12±.3

21±.6*†

8±2*

13±3*†

17±4*†

10±2*

19±10

8±1*

11±2*

18.5±9*

12±3

Transfer
Phase (Degrees)

Control

Low Flow

Normal Flow

24±12

53±8†

50±5†

80±46*

129±.34*

169±.32*

90±40*

140±33*

171±37*

88±42*

132±24*†

170±25*

80±17*

92±24*

210±198

(*p<0.05
compared to baseline, †=p<0.05
different from control.)

1. The left
panels show representative heart rate (upper panel) and blood pressure
(lower panel) from a control subject during static handgrip. The right
panels show corresponding representative heart rate (upper panel) and
blood pressure (lower panel) from a low flow POTS subject. Baseline
heart rate is increased in the POTS patient compared to control. Heart
rate and blood pressure increases with handgrip are attenuated in the
POTS patient.

The left panels
show percent changes in heart rate (upper panel) and blood pressure
(lower panel) averaged over all subjects. Control subjects are in black,
low flow POTS in red, normal flow POTS in green. Percent changes are
shown after 1 and 2 minutes of handgrip and during the recovery period.
There is an attenuation of the increase in heart rate and blood pressure
for low flow POTS. *=P<0.05 compared to control subjects.

The figure shows
percent changes from baseline in thoracic, splanchnic, pelvic, and calf
blood volumes during handgrip averaged over all subjects at 1 minute and
2 minutes after starting handgrip and during recovery. Central thoracic
blood volume increases for control but in neither POTS group at 1 minute
and remains different from control at 2 minutes of handgrip and during
recovery. Increased cardiac volume corresponds to a decrease in
splanchnic volume which is absent in POTS. *=P<0.05 compared to control.

The figure shows
percent changes in segmental blood flow. From top down changes in
thoracic, splanchnic, pelvic and leg (calf) are shown in order. Blood
flow increases for the central thoracic (CO) in healthy controls but not
in POTS at 1 minute of handgrip. CO does increase in normal flow POTS
patients at the second minute of handgrip. Percent change in splanchnic
blood flows are increased in POTS, while pelvic and calf segments are
variably affected in POTS subgroups. *=P<0.05 compared to control.

The figure shows
percent changes in segmental arterial resistance. From top down changes
in thoracic, splanchnic, pelvic and calf are shown in order. Total
peripheral resistance (thoracic resistance) was mildly increased in
control subjects but markedly increased in POTS patients. This was
generally associated with an increase in pelvic and calf resistance in
POTS compared to control. *=P<0.05 compared to control.

The Increase
in Central Blood Volume is Blunted in POTS
The normal increase in central blood volume during the exercise pressor
reflex is abolished in low flow POTS patients and attenuated in normal
flow POTS. In general there appears to be an overall reduction in
regional blood volume redistribution in low flow POTS.

Normal flow POTS
patients have blunting of blood volume redistribution that relates to
selective pooling in the splanchnic circulation. This limits the
increases in central blood volume during handgrip. Similar limitation of
central blood volume occurs during orthostatic stress.

Total
Peripheral Resistance rather than Cardiac Output Drives Regional Blood
Volume The most important
new finding in this study is that the exercise pressor reflex
produces a smaller pressor response in low flow POTS patients and that
the mechanism of the pressor response is shifted from the increased
cardiac output and central blood volume observed in control subjects to
increased vasoconstriction and peripheral resistance. Specifically,
in low flow POTS, the cardiac output component is essentially
abolished and the pressor response is completely driven by increased
peripheral resistance. In normal flow POTS vasoconstriction is more
selective and is deficient within the splanchnic regional circulation.
We have presented evidence for sympathoexcitation in POTS and others
have presented measurements of increased sympathetic nerve activity with
blunting of responses to diverse stimuli. We propose that the data
shown here support the theories that low flow POTS patients have
inappropriate sympathetic and adrenergic activation possibly driven by
central nervous system mechanisms controlling sympathetic outflow,
while normal flow POTS patients have reflex peripheral sympathetic
activation produced by selective splanchnic blood flow deficits.

Baroreflex
regulation of Heart Rate during Handgrip (Cardiovagal
Regulation):
As noted previously, HRV technique alone or combined with measurement of
blood pressure variability primarily estimates parasympathetic control
of heart rate. The difficulty in interpreting sympathetic change
is somewhat improved by using the low frequency to high frequency
ratios. In that regard, it is interesting that overall HRV power and low
frequency power, although decreased compared to control in low flow POTS
patients, is sustained or even increased during exercise. This is
different from results from control patients in whom heart rate
variability and by extension baroreflex gain are reduced by the
metaboreflex with similar findings in animal models. Sustained
sympathetic effects on the heart and are consistent with sustained
sympathetic cardiac contractility. In support, low flow POTS patients
have markedly increased cardiac afterload, no increase in cardiac
preload and sustained cardiac output suggesting increased contractility.
Therefore, it may be reasonable to infer that cardiac sympathetic
innervation remains relatively intact in POTS even though baroreflex
gain may be reduced.

On the other hand,
cardiovagal coherence is inadequate in low flow POTS at all times. This
indicates uncoupling between blood pressure and heart rate regulation

The Exercise
Pressor Reflex in POTS - Central Sympathetic Activation
The shift from a cardiac output driven exercise pressor response to an
arterial resistance-driven pressor response is similar to observations
made in congestive heart failure. In heart failure, baroreflexes are
markedly impaired with reductions in both sympathetic and cardiovagal
baroreflex sensitivities. As a result the ability of the arterial
baroreflex to buffer the muscle metaboreflex is severely attenuated .
In low flow POTS, the baroreflexes are also impaired with reductions in
both sympathetic and cardiovagal baroreflex sensitivities. The arterial
baroreflex buffers the vasoconstriction from the muscle metaboreflex and
mechanoreflex comprising the exercise pressor reflex by reducing this
peripheral vasoconstriction. Arguing by analogy, recent data concerning
heart failure indicate an important role for increased angiotensin II
and decreased neuronal nitric oxide activity in attenuating the
baroreflex. Increased angiotensin II and reduced nitric oxide are
features of low flow POTS.